Metabolic and Weight Loss Effects of Long‐Term Dietary Intervention in Obese Patients: Four‐Year Results

Objective: To investigate the contribution of meal and snack replacements for long‐term weight maintenance and risk factor reduction in obese patients. Research Methods and Procedures: Prospective, randomized, two‐arm, parallel intervention for 12 weeks followed by a prospective single‐arm 4‐year trial in a University Hospital clinic. One hundred patients, >18 years old and with a body mass index > 25 and ≤ 40 kg/m², were prescribed a 1200 to 1500 kcal/d control diet (Group A) or an isoenergetic diet, including two meal and snack replacements (vitamin‐ and mineral‐fortified shakes, soups, and bars) and one meal high in fruits and vegetables (Group B). Following a 3 months of weight loss, all patients were prescribed the same energy‐restricted diet (1200 to 1500 kcal) with one meal and one snack replacement for an additional 4 years. Results: All 100 patients were evaluated at 12 weeks. Mean percentage weight loss was 1.5 ± 0.4% and 7.8 ± 0.5% (mean ± SEM) for Groups A and B, respectively. At 12 weeks systolic blood pressure, plasma triacylglycerol, glucose, and insulin concentrations were significantly reduced in Group B, whereas no changes occurred in Group A. After 4 years, 75% of the patients were evaluated. Total mean weight loss was 3.2 ± 0.8% for Group A and 8.4 ± 0.8% (mean ± SEM) for Group B. Both groups showed significant improvement in blood glucose and insulin (p < 0.001), but only Group B showed significant improvement in triacylglycerol and systolic blood pressure compared to baseline values (p < 0.001). Discussion: Providing a structured meal plan via vitamin‐ and mineral‐fortified liquid meal replacements is a safe and effective dietary strategy for obese patients. Long‐term maintenance of weight loss with meal replacements can improve certain biomarkers of disease risk.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

Major Increase in Prevalence of Overweight and Obesity between 1987 and 2001 among Danish Adults

Objective: The aim of the study was to examine the secular trends in the prevalence of obesity (BMI ≥ 30.0 kg/m²) and overweight (25.0 ≤ BMI < 30.0 kg/m²) in Danish adults between 1987 and 2001. Research Methods and Procedures: The study included self‐reported weight and height of 10, 094 men and 9897 women 16 to 98 years old, collected in a series of seven independent cross‐sectional surveys. Prevalence and changes in prevalence of obesity and overweight stratified by sex and age groups were determined Results: The prevalence of obesity more than doubled between 1987 and 2001, in men from 5.6% to 11.8% [odds ratio (OR) = 2.3, 95% confidence interval (CI) = 1.9 to 2.8, p < 0.0001] and in women from 5.4% to 12.5% (OR = 2.6, 95% CI = 2.1 to 3.2, p < 0.0001), with the largest increase among the 16‐ to 29‐year‐old subjects (men, from 0.8% to 7.5%, OR = 10.2, 95% CI = 4.1 to 25.3, p < 0.0001; women, from 1.4% to 9.0% OR = 7.0, 95% CI = 3.5 to 14.1, p < 0.0001). Between 1987 and 2001, the prevalence of overweight increased from 34% to 40% in men and from 17% to 27% in women. Discussion: The prevalence of overweight and obesity in Denmark has increased substantially between 1987 and 2001, particularly among young adults, a development that resembles that of other countries. There is clearly a need for early preventive efforts in childhood to limit the number of obesity‐related complications in young adults.     

Disability,Arthritis, and Body Weight among Adults 45 Years and Older

Objectives : To examine the association between body weight and disability among persons with and without self‐reported arthritis. Research Methods and Procedures : Data were analyzed for noninstitutionalized adults, 45 years or older, in states that participated in the Behavioral Risk Factor Surveillance System. Self‐reported BMI (kilograms per meter squared) was used to categorize participants into six BMI‐defined groups: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), obese, class 1 (30 to <35), obese, class 2 (35 to <40), and obese, class 3 (≥40). Results : Class 3 obesity (BMI ≥ 40) was significantly associated with disability among participants both with and without self‐reported arthritis. The adjusted odds ratio (AOR) for disability in participants with class 3 obesity was 2.75 [95% confidence interval (CI) = 2.22 to 3.40] among those with self‐reported arthritis and 1.77 (95% CI = 1.20 to 2.62) among those without self‐reported arthritis compared with those of normal weight (BMI 18.5 to <25). Persons with self‐reported arthritis who were obese, class 2 (BMI 35 to <40) and obese, class 1 (BMI 30 to <35) and women with self‐reported arthritis who were overweight (BMI 25 to <30) also had higher odds of disability compared with those of normal weight [AOR = 1.72 (95% CI = 1.47 to 2.00), AOR = 1.30 (95% CI = 1.17 to 1.44), and AOR = 1.18 (95% CI = 1.06 to 1.32), respectively]. Discussion : Our findings reveal that obesity is associated with disability. Preventing and controlling obesity may improve the quality of life for persons with and without self‐reported arthritis.     

Economic evaluation of weight loss interventions in overweight and obese women

Objective: To conduct a clinical and economic evaluation of outpatient weight loss strategies in overweight and obese adult U.S. women. Research Methods and Procedures: This study was a lifetime cost‐use analysis from a societal perspective, using a first‐order Monte Carlo simulation. Strategies included routine primary care and varying combinations of diet, exercise, behavior modification, and/or pharmacotherapy. Primary data were collected to assess program costs and obesity‐related quality of life. Other data were obtained from clinical trials, population‐based surveys, and other published literature. This was a simulated cohort of healthy 35‐year‐old overweight and obese women in the United States. Results: For overweight and obese women, a three‐component intervention of diet, exercise, and behavior modification cost $12,600 per quality‐adjusted life year gained compared with routine care. All other strategies were either less effective and more costly or less effective and less cost‐effective compared with the next best alternative. Results were most influenced by obesity‐related effects on quality of life and the probabilities of weight loss maintenance. Discussion: A multidisciplinary weight loss program consisting of diet, exercise, and behavior modification provides good value for money, but more research is required to confirm the impacts of such programs on quality of life and the likelihood of long‐term weight loss maintenance.     

Effect of Pramlintide on Weight in Overweight and Obese Insulin‐Treated Type 2 Diabetes Patients

Objective: Several randomized, placebo‐controlled, double‐blind trials in insulin‐treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide reduces hemoglobin (Hb)A_1c with concomitant weight loss. This analysis further characterizes the weight‐lowering effect of pramlintide in this patient population. Research Methods and Procedures: This pooled post hoc analysis of two long‐term trials included all patients who were overweight/obese at baseline (BMI > 25 kg/m²), and who were treated with either 120 μg pramlintide BID (n = 254; HbA_1c 9.2%; weight, 96.1 kg) or placebo (n = 244; HbA_1c 9.4%; weight, 95.0 kg). Statistical endpoints included changes from baseline to week 26 in HbA_1c, body weight, and insulin use. Results: Pramlintide treatment resulted in significant reductions from baseline to week 26, compared with placebo, in HbA_1c and body weight (both, p < 0.0001), for placebo‐corrected reductions of ?0.41% and ?1.8 kg, respectively. Approximately three times the number of patients using pramlintide experienced a ≥5% reduction of body weight than with placebo (9% vs. 3%, p = 0.0005). Patients using pramlintide also experienced a proportionate decrease in total daily insulin use (r = 0.39, p < 0.0001). The greatest placebo‐corrected reductions in weight at week 26 were observed in pramlintide‐treated patients with a BMI >40 kg/m² and in those concomitantly treated with metformin (both, p < 0.001), for placebo‐corrected reductions of ?3.2 kg and ?2.5 kg, respectively. Discussion: These findings support further evaluation of the weight‐lowering potential of pramlintide in obese patients with type 2 diabetes.     

Longitudinal Analyses among Overweight,Insulin Resistance,and Cardiovascular Risk Factors in Children

Objective: It has been questioned whether insulin resistance or obesity is the central abnormality contributing to the cardiovascular risk factors dyslipidemia and hypertension in obesity. Research Methods and Procedures: We studied weight status [SD score (SDS)‐BMI], lipids (triglycerides, low‐density lipoprotein‐ and high‐density lipoprotein‐cholesterol), blood pressure, and insulin resistance index [as homeostasis model assessment (HOMA) model] over a 1‐year period in 229 obese white children (median age 12 years). Results: Any degree of decrease in HOMA was associated with significant decreases in triglycerides (p < 0.001), systolic blood pressure (p < 0.001), and diastolic blood pressure (p < 0.001), whereas the children with different changes in HOMA did not differ significantly in their weight changes. Only the children in the highest quartile of weight reduction (decrease in SDS‐BMI > 0.5) demonstrated a significant decrease in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and triglycerides (p = 0.012), and an increase in high‐density lipoprotein‐cholesterol (p = 0.023), whereas with a lower degree of weight loss, there were no significant changes in cardiovascular risk factors. In contrast with a lower degree of weight loss, a reduction of >0.5 SDS‐BMI was associated with a significant decrease in HOMA (p < 0.001). Discussion: Because blood pressure and triglycerides decreased with any degree of decrease in HOMA, independently of changes in weight status, these findings support the hypothesis that insulin resistance is the central abnormality contributing to these cardiovascular risk factors. Therefore, improving insulin resistance seems more important than reducing overweight to prevent or treat hypertension and dyslipidemia in obese children.     

Epidemiology of Overweight and Obesity in a Greek Adult Population: the ATTICA Study

Objective: To evaluate the status of overweight and obesity in a Greek random sample. Research Methods and Procedures: From 2001 to 2002, 1514 men (20 to 87 years old) and 1528 women (20 to 89 years old) were enrolled into the study. Among several sociodemographic, lifestyle, and bioclinical factors, anthropometric characteristics were also recorded. Overweight and obesity were defined according to the World Health Organization classification. Results: The prevalences of overweight and obesity were 53% and 20% in men and 31% and 15% in women (p for gender differences < 0.05). The age‐adjusted peak prevalence of obesity was observed in men older than 40 years old and women between 50 and 59 years old (Bonferonni α < 0.001). Central obesity prevailed in 36% of men and 43% of women (p for gender differences < 0.001). Obesity varied from 10% in rural to 25% in urban areas, but this difference was explained mainly by differences in occupational status (p = 0.9). Moreover, obese and overweight participants were older, less educated, more frequently sedentary, consumed higher quantities of alcoholic beverages, and were devoted to an unhealthier diet as compared with those of normal weight (all p < 0.05). A positive association was also observed between BMI and diastolic and systolic blood pressures, total cholesterol, triglycerides, and glucose levels (all p < 0.001). Discussion: Overweight and obesity seem to be a great health problem in the Greek population, especially in middle‐aged and older adults. Unfavorable lifestyle habits, low education, and the classical cardiovascular risk factors were associated with the prevalence of these health conditions.     

Longitudinal Relationship between Elapsed Time in the Action Stages of Change and Weight Loss

Objective: The objective of this study was to examine the longitudinal relationship between the elapsed time in the action and maintenance stages of change for multiple target behaviors and weight loss or gain. Research Methods and Procedures: The research design was a prospective cohort study of overweight and obese primary care patients randomized to an obesity management intervention based on the Transtheoretical Model and a chronic disease paradigm. The target behaviors included increased planned exercise and usual physical activity, decreased dietary fat, increased fruit and vegetable consumption, and increased dietary portion control. The participants were 329 middle‐aged men and women with elevated body mass indices recruited from 15 primary care practices in Northeastern Ohio; 28% of the participants were African Americans. The main outcomes were weight loss (5% or more) or weight gain (5% or more) after 18 or 24 months of follow‐up. Results: There were significant (p < 0.05) longitudinal relationships between the number of periods (0 to 4) in action or maintenance for each of the five target behaviors, or a composite score taken across the five target behaviors, and weight loss. In all cases, there was a significant (p < 0.05) stepped (graded) relationship between the time in action or maintenance and weight loss (or gain). Discussion: The data support the concept of applying the Transtheoretical Model to the problem of managing obesity in primary care settings. The remaining challenge is to identify those factors that reliably move patients into the action and maintenance stages for long periods.     

The Canadian Obesity Epidemic: An Historical Perspective

Objective: To examine temporal trends in stature, body mass, body mass index (BMI), and the prevalence of overweight and obesity in Canada. Research Methods and Procedures: Data for adults 20 to 64 years of age were compared across eight Canadian surveys conducted between 1953 and 1998. Temporal trends in stature and body mass were examined using regression, and changes in weight‐for‐height were expressed as changes from 1953. BMI data were available from 1970 to 1972 to examine changes in overweight and obesity. Qualitative changes in the BMI distribution were examined using Tukey mean‐difference plots. Results: Significant temporal trends in stature and body mass have occurred since 1953 in Canada. Median stature increased 1.4 cm/decade in men and 1.1 cm/decade in women, whereas median body mass increased 1.9 kg/decade in men and 0.8 kg/decade in women. Increases in the 75th percentile of body mass were larger than the median. The average weight‐for‐height increased 5.1% in men and 4.9% in women from 1953. Furthermore, the prevalences of overweight and obesity have increased from 40.0% and 9.7% in 1970–1972 to 50.7% and 14.9% in 1998, respectively. The entire BMI distribution has shifted to the right since 1970–1972 and has become more skewed to the right for men than for women. Discussion: There have been significant increases in stature and body mass in Canada over the last 45 years. Body mass has increased more than stature, particularly in the upper percentiles, which has resulted in the currently observed high prevalences of overweight and obesity.     

Use of Very Low-Calorie Diet in Preoperative Weight Loss: Efficacy and Safety

PEKKARINEN, TUULA, PERTTI MUSTAJOKI. Use of very low-calorie diet in preoperative weight loss: Efficacy and Safety. We report the efficacy of a very low-calorie diet (VLCD)-based weight reduction program in patients with morbid obesity whose elective surgery had been postponed because of being overweight. The safety of weight loss on the immune system will also be evaluated. Thirty patients (mean age, 50 years; weight, 125 kg; BMI, 44 kg/m2) were treated. The program consisted of a 7-week to 24-week VLCD period, supported by individual sessions with a therapist, and of a refeeding period of 1 month before surgery. Two patients discontinued, and the mean weight loss of the remaining 28 patients was 19. 6 kg (15% of initial weight). In 23 patients, weight loss was 10% or more of the initial weight. After weight loss, 15 patients underwent surgery, 4 patients did not need an operation, and the remaining 9 patients were not operated on for various reasons. The numbers of circulating leukocytes, neutrophils, basophils, monocytes, CD3+, CD4+, CD8+, and natural killer cells did not change significantly by the ninth week on VLCD or by the end of the program. However, there was a significant (p<0. 05) decrease in the immunoglobulinM serum concentration during the program. In conclusion, a VLCD program is suitable for preoperative weight reduction in morbid obesity and seems not to compromise the immune system.     

Decreased Glucagon‐like Peptide 1 Release after Weight Loss in Overweight/Obese Subjects

Objective: Postprandial glucagon‐like peptide 1 (GLP‐1) release seems to be attenuated in obese subjects. Results on whether weight loss improves GLP‐1 release are contradictory. The aim of this study was to further investigate the effect of weight loss on basal and postprandial GLP‐1 release in overweight/obese subjects. Research Methods and Procedures: Thirty‐two overweight/obese subjects participated in a repeated measurement design before (BMI, 30.3 ± 2.8 kg/m²; waist circumference, 92.6 ± 7.8 cm; hip circumference, 111.1 ± 7.4 cm) and after a weight loss period of 6 weeks (BMI, 28.2 ± 2.7 kg/m²; waist circumference, 85.5 ± 8.5 cm; hip circumference, 102.1 ± 9.2 cm). During weight loss, subjects received a very‐low‐calorie diet (Optifast) to replace three meals per day. Subjects came to the laboratory fasted, and after a baseline blood sample, received a standard breakfast (1.9 MJ). Postprandially, blood samples were taken every one‐half hour relative to intake for 120 minutes to determine GLP‐1, insulin, glucose, and free fatty acids from plasma. Appetite ratings were obtained with visual analog scales. Results: After weight loss, postprandial GLP‐1 concentrations at 30 and 60 minutes were significantly lower than before weight loss (p < 0.05). Glucose concentrations were also lower, and free fatty acids were higher compared with before weight loss. Ratings of satiety were increased, and hunger scores were decreased after weight loss (p < 0.05). Discussion: In overweight/obese subjects, GLP‐1 concentrations after weight loss were decreased compared with before weight loss, and nutrient‐related stimulation was abolished. This might be a response to a proceeding negative energy balance. Satiety and GLP‐1 seem to be unrelated in the long term.     

Amount of Food Group Variety Consumed in the Diet and Long‐Term Weight Loss Maintenance

Objective: Decreases in variety of foods consumed within high‐fat‐dense food groups and increases in variety of foods consumed within low‐fat‐dense food groups are associated with lower energy intake and greater weight loss during obesity treatment and may assist with weight loss maintenance. This study examined food group variety in 2237 weight loss maintainers in the National Weight Control Registry, who had lost 32.2 ± 18.0 kg (70.9 ± 39.5 lbs) and maintained a weight loss of at least 13.6 kg (30 lbs) for 6.1 ± 7.7 years. Research Methods and Procedures: At entry into the registry, registry members completed a food frequency questionnaire from which amount of variety consumed from different food groups was assessed. To provide a context for interpreting the level of variety occurring in the diet of registry participants, food group variety was compared between registry participants and 96 individuals who had recently participated in a behavioral weight loss program and had lost at least 7% of initial body weight. Results: Registry members reported consuming a diet with very low variety in all food groups, especially in those food groups higher in fat density. Registry participants consumed significantly (p < 0.001) less variety within all food groups, except fruit and combination foods, than recent weight losers after 6 months of weight loss treatment. Discussion: These results suggest that successful weight loss maintainers consume a diet with limited variety in all food groups. Restricting variety within all food groups may help with consuming a low‐energy diet and maintaining long‐term weight loss.     

Bupropion for Weight Loss: An Investigation of Efficacy and Tolerability in Overweight and Obese Women

Objective: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. Research Methods and Procedures: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m²) women were included. The core component of the study was a randomized, double‐blind, placebo‐controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double‐blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single‐blind follow‐up treatment for a total of 2 years. Results: Subjects receiving bupropion achieved greater mean weight loss (last‐observation‐carried‐forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% ± 3.4% (n = 25) for bupropion treatment compared with 1.3% ± 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% ± 3.1% (n = 18) vs. 1.6% ± 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% ± 5.6% with fat accounting for 73.5% ± 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well‐tolerated in this sample. Discussion: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.     

Bupropion SR Enhances Weight Loss: A 48‐Week Double‐Blind,Placebo‐ Controlled Trial

Objective: To critically examine the efficacy of bupropion SR for weight loss. Research Methods and Procedures: This 24‐week multicenter, double‐blind, placebo‐controlled study randomized obese adults to placebo, bupropion SR 300, or 400 mg/d. Subjects were counseled on energy‐restricted diets, meal replacements, and exercise. During a 24‐week extension, placebo subjects were randomized to bupropion SR 300 or 400 mg/d in a double‐blinded manner. Results: Of 327 subjects enrolled, 227 completed 24 weeks; 192 completed 48 weeks. Percentage losses of initial body weight for subjects completing 24 weeks were 5.0%, 7.2%, and 10.1% for placebo, bupropion SR 300, and 400 mg/d, respectively. Compared with placebo, net weight losses were 2.2% (p = 0.0468) and 5.1% (p < 0.0001) for bupropion SR 300 and 400 mg/d, respectively. The percentages of subjects who lost ≥5% of initial body weight were 46%, 59%, and 83% (p vs. placebo < 0.0001) for placebo, bupropion SR 300, and 400 mg/d, respectively; weight losses of ≥10% were 20%, 33%, and 46% (p vs. placebo = 0.0008) for placebo, bupropion SR 300, and 400 mg/d, respectively. Withdrawals, changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks. Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5% and 8.6% for bupropion SR 300 and 400 mg/d, respectively. Discussion: Bupropion SR 300 and 400 mg/d were well‐tolerated by obese adults and were associated with a 24‐week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.     

The Relationship of Health Outcomes to Improvement in BMI in Children and Adolescents

Objective: To evaluate the clinical outcomes of patients participating in an outpatient program for managing childhood and adolescent obesity. Research Methods and Procedures: Based on a retrospective chart review, 394 physician‐referred obese youth (BMI > 95th percentile), 5 to 19 years of age, were treated in an interdisciplinary, family‐centered, behavioral weight management program in a hospital‐based outpatient setting. Treatment included group exercise, parent education, and behavioral intervention therapies to improve diet and physical activity. Results: A total of 177 (45%) completed the initial phase of treatment (mean duration = 5.6 months). For the completion group, there were significant improvements (all p < 0.001) in weight (?2.0 ± 4.9 kg), BMI (?1.7 ± 1.9 kg/m²), and BMI z score (?0.15 ± 0.15), without interfering with growth (height, 2.2 ± 1.3 cm; p < 0.001). Significant improvement was also found for blood pressure, total cholesterol, low‐density lipoprotein (LDL)‐cholesterol, triglycerides, insulin, and aerobic fitness. At onset of treatment, 134 (84%) patients had abnormal fasting insulin concentration, 88 (50%) had abnormal total cholesterol, 14 (8%) had abnormal diastolic blood pressure, and 69 (40%) had abnormal LDL‐cholesterol. At the end of treatment, a significant proportion of patients with baseline abnormal blood pressure, total cholesterol, and LDL‐cholesterol had normal values (p < 0.001). A decrease in BMI z score was associated with significant improvements in insulin and lipid values (all p < 0.05). Discussion: We have demonstrated that a modest decrease in BMI in an ongoing clinical pediatric weight management program is accompanied by significant improvements in related health measures. These results may be helpful in counseling families with overweight children and adolescents.     

Topiramate: Long‐Term Maintenance of Weight Loss Induced by a Low‐Calorie Diet in Obese Subjects

Objective: To examine the safety and efficacy of topiramate (TPM) for maintaining weight following a low‐calorie diet. Research Methods and Procedures: Obese subjects (30 ≤ BMI < 50 kg/m²) 18 to 75 years old received a low‐calorie diet for 8 weeks. Those who lost ≥8% of their initial weight received TPM (96 or 192 mg/d) or placebo; all were on a lifestyle modification plan. Sixty weeks of medication were planned. Sponsor ended study early to develop a new controlled‐release formulation with the potential to enhance tolerability and simplify dosing in this patient population. Efficacy was analyzed in subjects who completed 44 weeks of treatment before study termination. Results: Of the 701 subjects enrolled, 80% lost ≥8% of their initial body weight and were randomized; 293 were analyzed for efficacy. Most withdrawals were due to premature termination of the study. Subjects receiving TPM lost 15.4% (96 mg/d) and 16.5% (192 mg/d) of their enrollment weight by week 44, compared with 8.9% in the placebo group (p < 0.001). Subjects on TPM continued to lose weight after the run‐in, whereas those on placebo regained weight. Significantly more TPM subjects lost 5%, 10%, or 15% of their randomization weight than placebo. Most adverse events were related to the central nervous system. Discussion: During a treatment period of 44 weeks, TPM was generally well tolerated, and subjects maintained weight loss initially achieved by a low‐calorie diet—and produced additional clinically significant weight loss beyond that achieved by a low‐calorie diet.     

Weight Loss,Weight Maintenance,and Improved Cardiovascular Risk Factors after 2 Years Treatment with Orlistat for Obesity

Objective: To determine the effect of orlistat, a new lipase inhibitor, on long‐term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity‐related risk factors. Research Methods and Procedures: This was a 2‐year, multicenter, randomized, double‐blind, placebo‐controlled study. Obese patients (body mass index 28 to 43 kg/m²) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured. Results: Orlistat‐treated patients lost significantly more weight (p < 0.001) than placebo‐treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p < 0.001 for orlistat 120 mg). Several obesity‐related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat‐treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self‐limiting and usually occurred early during treatment. Discussion: Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.